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HPJ Pharmacy Bulletin Volume 2/ 2013
Page | 1
PPhhaarrmmaaccyy BBuulllleettiinn JJuullyy 22001133 EEddiittiioonn ((VVoolluummee 22//22001133))
HHoossppiittaall PPuuttrraajjaayyaa PPhhaarrmmaaccyy DDeeppaarrttmmeenntt
1. Adenovirus
The Adenovirus is an extremely
hardy virus, ubiquitous in
human and animal populations, survives long periods outside a
host, and is endemic throughout
the year. Page 2
2. Breezhaler
According to a World Health
Organization (WHO) report,
COPD is silent killer that claims
nearly three million lives
annually worldwide. Page 6
3. Medication
nnSafety
4. LASA
Look-alike sound-alike
medications Page 12
Counterchecking should be
practiced in every stage of
dispensing, not only before
medication is served or given to
the patient. Page 9
EEddiittoorriiaall BBooaarrdd
AAddvviissoorr:: PPnn KKaammaarruunnnneessaa MMookkhhttaarr AAhhmmaadd
EEddiittoorriiaall BBooaarrdd::
CCiikk SSaallmmii AAbbdduull RRaazzaakk
PPnn NNaaddiiaahh MMoohhaammeedd KKhhaazziinn
CCiikk SShhaarriiffaahh SShhaaffaawwaattii BBtt SSyyeedd MMoohhdd HHaammddaann
HHeemmaannaanntthhiinnii SSuuppppiiaahh
SSeeww JJuunn YYaann
MMuuhhaammaadd NNoorrddiinn BBiinn AAzzmmaann
LLiimm CChhiiaa YYiinn
HPJ Pharmacy Bulletin Volume 2/ 2013
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An extremely hardy virus,
adenovirus is ubiquitous in human and
animal populations, survives long periods
outside a host, and is endemic throughout
the year.1 Adenoviruses are medium-sized
(90-100 nm), non-enveloped icosahedral
viruses with double-stranded
deoxyribonucleic acid (DNA).2 Possessing
52 serotypes, adenovirus is recognised as the
aetiologic agent of various diverse
syndromes. It is transmitted via direct
inoculation to the conjunctiva, a faecal-oral
route, aerosolised droplets, or exposure to
infected tissues or blood. Adenoviruses are
relatively resistant to chemical and physical
agents and to adverse pH conditions and can
live for a very long time outside the body.1, 2,
3 The structure and colourised transmission
electron micrograph (TEM) of adenovirus
are shown in the Figure 1.1 and Figure 1.2
respectively.
Figure 1.1: The Structure of Adenovirus
Figure 1.2: Colourised Transmission Electron Micrograph (TEM) of Adenovirus
Adenovirus
HPJ Pharmacy Bulletin Volume 2/ 2013
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Adenoviral infections affect babies
and young children much more often as
compared to adults. Childcare centers and
schools sometimes have multiple cases of
respiratory infections and diarrhoea caused
by adenovirus. The virus is capable of
infecting multiple organ systems; however,
most infections are asymptomatic. Even if a
person has adenovirus, it does not
necessarily mean that this virus it is causing
the particular illness that the person has. A
person can shed the virus for months or
years and not have symptoms. Adenovirus is
often cultured from the pharynx and stool of
asymptomatic children, and most adults
have measurable titers of anti-adenovirus
antibodies, implying prior infection.
Adenovirus infections can be identified by
using antigen detection, polymerase chain
reaction (PCR) assay, virus isolation, and
serology. Adenovirus is known to be
oncogenic in rodents but not in humans.2, 3, 4
The majority of us will have
experienced at least one adenoviral infection
by age 10. Because of the many types of
adenoviral infections, a child may be
repeatedly infected with different variants of
the virus. Most paediatric adenovirus
respiratory infections are mild and
indistinguishable from other viral causes.
However, in a few children, the disease can
be severe and results in substantial
morbidity. We describe the epidemiologic,
clinical, radiologic features and outcome of
adenovirus lower respiratory tract infections
(LRTI) in Aboriginal and Non-Aboriginal
children in Manitoba, Canada during the
years 1991 and 2005.5
The symptoms of an adenovirus
infection are similar to the ones associated
with a common cold. Children who are sick
might experience stuffy or runny nose, as
well as sore throat, infection of the breathing
tubes in their lungs, eyelid inflammation,
fever, middle ear infection, or pneumonia.
Some children might have a harsh cough
similar to those with whooping cough.5
At times there may be some bleeding
into the covering of their swollen eyes.
While the adenovirus might cause a person's
eyes to look very ill, their vision remains
unaffected. Children who are infected with
some strains of the adenovirus may develop
HPJ Pharmacy Bulletin Volume 2/ 2013
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inflammation of their stomach and intestinal
tract, something that has the potential to
cause abdominal cramping and diarrhoea. 4, 6
The adenovirus might infect a
person's bladder, cause blood in their urine,
and painful urination. In some occasions, the
virus causes an infection either in or around
a person's brain. In children who have
undergone an organ transplant, or who
experience other conditions resulting in a
weakened immune system, adenovirus
infections are something that can be very
severe and have the potential to result in
overwhelming infection, or even death.
After a child has been exposed to an
adenovirus, there is an incubation period of
2 to 14 days before they experience
symptoms.4, 6
Most adenovirus infections are mild
and typically require symptomatic
treatments. To date, specific therapy for
adenovirus infection, other than supportive
and symptomatic treatment, remains a
matter of debate. Fortunately, most of
adenovirus infections are self-limited in the
setting of a normal immune response and do
not require any specific therapy. 3, 7
There are no approved antiviral
agents with proven efficacy for the treatment
of severe adenovirus disease, nor are there
are prospective randomised, controlled trials
of potentially useful anti-adenovirus
therapies. Apparent clinical success in the
treatment of severe adenovirus disease is
limited to a few case reports and small
series. The best clinical outcomes were
achieved by the use of intravenous ribavirin
and cidofovir. 3, 7
Ribavirin, a guanosine analogue, has
broad antiviral activity against both RNA
and DNA viruses, including documented
activity against adenovirus in-vitro.
Intravenous ribavirin is the treatment of
choice for infection with hemorrhagic fever
viruses. The most common adverse effect of
intravenous ribavirin is reversible mild
anaemia. The use of cidofovir in severe
adenovirus infection has been limited by
adverse effects, the most significant of
which is nephrotoxicity.3, 7
In addition, there are two other
antiviral agents including ganciclovir and
vidarabine, which have been used to treat
severe adenovirus infections, especially in
immunocompromised patients. The use of
these medications has been based on case
reports and clinical studies, but no
prospective controlled treatment trials have
been conducted. 3, 7, 8
There is no standard ribavirin dosage
regimen or an agreed consensus between
specialists and Head of Paediatric
Department from Hospital Tuanku Jaafar,
Seremban and it is an off-label use for
adenovirus infections. The regimen is given
for 10 days with the dose of 30mg/kg TDS
(From day 1 to day 4); follow by 15mg/kg
TDS (from day 5 to day 10). There are 2
brands of ribavirin available in the market,
namely Rebetol® (capsule) and Copegus
®
(film-coated tablet). Copegus®
tablet is not
recommended to be crushed and made into
syrup as it is film-coated tablet. As for
Rebetol® capsule, it can be made into
syrup.9,10,11
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There is a vaccine available for the
treatment of adenovirus and is indicated for
active immunisation of populations aged 17
to 50 years old for the prevention of febrile
acute respiratory disease caused by
adenovirus types 4 and 7.3
Oral capsule
Ribavirin 200mg per capsule
(Rebetol®)
Film-coated
tablet
Ribavirin 200mg per tablet
(Copegus®)
Day Treatment dose of ribavirin for
adenovirus positive (off-label use)9
1-4 30mg/kg TDS
5-10 15mg/kg TDS
– Note: Ribavirin 200mg tablet (Copegus®) is not
recommended to be crushed and made into
syrup10,11
HPJ Pharmacy Bulletin Volume 2/ 2013
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HANDIHALER VS BREEZHALER
Recent statistics showed that approximately
448,000 people in Malaysia suffer from
moderate to severe Chronic Obstructive
Pulmonary Disease (COPD). COPD is
already ranked as the 5th cause of death
worldwide. According to a World Health
Organization (WHO) report, this silent killer
claims nearly three million lives annually
worldwide. COPD is a progressive disease
that makes it hard to breathe. "Progressive"
means the disease gets worse over time.
According to GOLD, long acting B2 agonist
(LABA) and long acting anti-cholinergic are
the preferable agents as bronchodilator
therapy for first line management of COPD1.
Tiotropium differs from other anti-
cholinergics in its functional relative
selectivity and higher affinity for muscarinic
receptor subtypes. Indacaterol is a partial
agonist at the human beta2-adrenergic
receptor with nanomolar potency which has
a rapid onset of action and a long duration of
action2. Once-daily Indacaterol is an
effective 24-hour bronchodilator that
improves symptoms and health status and
confers clinical improvements over a twice-
daily 12h LABA as a treatment for patients
with moderate to severe COPD3. It is likely
that once-daily dosing of an ultra LABA
will lead to increased convenience for the
patients, which may also lead to
enhancement of compliance, and may have
advantages leading to improved overall
clinical outcomes in patients with COPD4.
For optimal efficacy, an inhaler should
deliver doses consistently and be easy for
patients to use with minimal instructions.
Indacaterol is a novel, inhaled, once-daily,
ultra-long-acting β2-agonist delivered by a
single-dose DPI known as the Breezhaler®
for maintenance treatment in COPD. The
other once-daily inhaled bronchodilator is
the anti-cholinergic, Tiotropium, delivered
by a single-dose DPI called the
HandiHaler®.
Breezhaler
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Handihaler Technique:
Breezhaler Technique:
STEPS FOR APPROPRIATE USE OF
THE HANDIHALER DEVICE
1. Remove capsule from blister
package
2. Open dust cap and mouthpiece
and place capsule in center
chamber
3. Close mouthpiece and dust cap
and hold device upward
4. Press the piercing button once
5. Exhale fully without device in
mouth
6. Inhale slowly and deeply with
device in mouth and lips sealed
around mouthpiece (should hear
capsule vibrate)
7. Hold breath as long as possible
8. Repeat steps 5 through 7 again to
ensure all medication has been
administered
9. Open dust cap and mouthpiece to
discard capsule and close
mouthpiece and dust cap
BREEZHALER TECHNIQUES
1. Remove capsule
2. Open inhaler and place the capsule
into the capsule chamber.
3. Close inhaler until you hear a
‘click’.
4. Pierce the capsule by firmly
pressing both side buttons at the
same time.
5. Breathe out before placing the
mouthpiece in your mouth.
6. Close your lips firmly around the
device and breathe in rapidly but
steadily & deeply.
7. Hold breath for 5-10 sec, and then
breathe out normally. If there’s
powder left in the capsule repeat
step 5-7.
8. Open mouthpiece and remove the
empty capsule. Discard the capsule
and reload a new capsule for the
next dose.
HPJ Pharmacy Bulletin Volume 2/ 2013
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[Table 1 shows a brief comparison between Handihaler and Breezhaler]
Table 1
Characteristics Handihaler Breezhaler
Drug Tiotropium Bromide Indacaterol
Classification Long Acting Anti-cholinergic Long Acting β2 Agonist
Strength
Available 18 mcg 150μg & 300μg
Dose Once daily
Onset of Action 30 min 5 min
Cost ++ +
Mechanism of
Action
It blocks muscarinic cholinergic
receptors, without specificity for
subtypes, resulting in a decrease in
the formation of cyclic guanosine
monophosphate (cGMP). Most likely
due to actions of cGMP on
intracellular calcium, this results in
decreased contractility of smooth
muscle.
Stimulation of ß2 adrenergic receptors
of bronchial smooth muscle cells
induces relaxation by activation of the
Gs-adenylyl cyclase-cAMP-PKA
pathway
Duration of
Action 24 Hours
Common
adverse effects
Upper respiratory tract infection,
dry mouth, Sinusitis
Nasopharyngitis, cough, muscle spasm,
upper respiratory tract infection
HPJ Pharmacy Bulletin Volume 2/ 2013
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1. Cefuroxime tablet? Or Fusidic acid
tablet?
Within a short period of three
months, 2 separate cases of Fusidic acid
250mg tablet wrongly filled as Cefuroxime
250mg tablet have occurred. In both cases,
the errors have by-passed the pharmacists
who filled the medication and also the
pharmacists who counterchecked the trolley.
The medications in the trolley were brought
forward to the ward and the errors were
finally detected by the nurses on duty.
Recommendation:
Look-alike medications should be notified to
all working personnel through newsletter
(i.e. Australian Alert, Medication Safety
Alert). Furthermore, such medications can
also be brought into attention during the
once a month morning assembly. This can
hopefully increase the awareness of the
pharmacist who are counterchecking and
subsequently reduce the error.
2. Under-treatment?
Benzylpenicillin was prescribed for a
paediatric patient aged 3 years and 1 month.
The doctor’s plan is to initiate penicillin at
100,000IU per dose QID and the weight of
the child of 11.5kg, therefore the supposed
dose of penicillin is 1,150,000IU QID.
However, dose of 115,000IU QID was
ordered in Fisicien system. The error was
undetected by the pharmacist who screened
the prescription and was carried forward to
the ward. In the ward, although the doctor
has noted in the medication chart the correct
dose of 1,150,000IU QID, but the nurse in-
charge has failed to notice the disparity. On
day 8 of the regimen, the error was finally
detected by the nurse and doctor was
consulted for confirmation.
Medication Safety
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Recommendation:
It is recommended that all drug orders to be
verified before medications are
administered. ASHP recommends that
nurses should carefully review original
medication orders before administration of
the first dose and compare them with the
medications dispensed.
Apart from that, counterchecking in the
pharmacy should also be enforced. This can
be improved by including the weight of
pediatric patients on the label. With the body
weight on the label, both the
counterchecking pharmacist and the nurses
in charge can be notified. In this case, the
counterchecking pharmacist can recalculate
the dose and the nurses in-charge can
reconfirm the body weight of the patient.
3. Lack of communication
Clonazepam 0.5 mg tablet was
intended for an eight month and seven days
old baby but 3.5mg Clonazepam tablet was
ordered. The error was undetected by the
pharmacist who screened the prescription.
As the medication is a dangerous drug and
under the list of floor stock, no filling and
counter-checking was done following
verification of the prescription. However,
the nurse in-charge has tried to confirm the
disparity between the orders. But the doctor
was not able to clarify the doubt and the
nurse carried on with the 3.5mg Clonazepam
tablet.
Recommendation:
Nurse should consult medical officers
directly if no appropriate action was taken
by the house officers. Any discrepancy
between clinical notes and drug chart should
be reconfirmed and clarified.
Prescription charts are necessarily in parallel
to the use of an electronic system in order to
force the staffs to develop interdisciplinary
collaboration and procedures that allow
immediate feedback control both among
prescribers and between prescribers and
other staff. (British Journal of Clinical
Pharmacology, March 18, 2009)
4. Look-alike-sound-alike
Maxitrol? Or Maxidex? Gutt.
Maxidex (Dexamethasone 0.1%) was
prescribed by an ophthalmology specialist
but Gutt. Maxitrol (Dexamethasone 0.1% +
Neomycin sulphate + Polymycin B sulphate)
was provided. The medication was filled
HPJ Pharmacy Bulletin Volume 2/ 2013
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wrongly and managed to escape counter-
checking by the pharmacist. The patient was
discharged with Maxitrol and the mistake
was not noticed until the next day, when the
patient went for a follow-up with the
specialist. However, the patient had not used
the eye drop.
Recommendation:
With the enormous number of medications
available in the market, potential for error
due to the confusing drug names (non-
proprietary names and proprietary names) is
significant, more so with the look-alike
packaging.
Emphasis on the need to carefully read the
label each time a medication is accessed and
again prior to administration instead of
relying on visual recognition, location, or
other less specific cues is recommended.
Using labeling techniques that can
conspicuously differentiate LASA products
can be implemented. For example: use
boldface and colour differences on labels,
storage bins and shelves, computer screens
and medication administration records.
(WHO Look-Alike Sound-Alike Medication
Names. May 2007)
5. Trimethoprim Overdose
With an infant’s body weight of
3.82kg at 1 month old, Trimethoprim
10mg/ml syrup 76mg was given. The infant
was overdosed by 10 times with the
intended dose being 7.6mg at night (2mg/kg
for urinary tract infection prophylaxis). 7.6
ml of TMP syrup was given ON for 4 days
instead of 0.76 ml ON, and the infant was
brought to the Emergency department due to
profuse vomiting after taking the
medication.
Recommendation:
As discussed previously in the case
regarding Benzylpenicillin, it is important to
stress about the enforcement of
counterchecking. Counterchecking should
be practiced in every stage of dispensing,
not only before medication is served or
given to the patient. Each and every staff in
the Pharmacy Department as well other
HealthCare professionals plays a role in
making sure that the right medication is
given to the right patient, at the right dose
and the right frequency.
HPJ Pharmacy Bulletin Volume 2/ 2013
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From left-right: Alfacalcidol 0.25mcg
tablet & Alfacalcidol 1 mcg tablet
capsules.
Which micardis?
Look-Alike Medications
The B-creams The Alfacalcidol family
Same flags but different doses
Be or not to Bea?
From left-right: Telmisartan 40mg
tablet & Telmisartan 80 mg tablet
From left-right: Betamethasone 0.1% w/v
eye/ear drops & Gentamicin 0.3% w/v eye/ear
drops
From top-bottom: Gentamicin 0.1%
cream & Miconazole 2% cream
LASA (Look-Alike Sound-Alike Medications)
HPJ Pharmacy Bulletin Volume 2/ 2013
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The Chlorhexidines
The Risperdals
From left-right: Chlorhexidine in Alcohol 1:2000
solution, Chlorhexidine in Aqueous 1:2000 solution
& Chlorhexidine in Alcohol 1:200 solution
From left-right: Mist Sodium Citrate
3g/10ml & Mist Potassium Chloride
1g/15ml
“MIST-aken” bottle Which is the correctXIDINE?
From left-right:Risperdal® Risperidone 25mg
injection & Risperdal® Risperidone 37.5mg
injection
From top-bottom: Potassium Permanganate
1.5% solution (as soaks) & Potassium
Permanganate 5% solution (as bath)
As soak or as bath?
HPJ Pharmacy Bulletin Volume 2/ 2013
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From left-right: CoAprovel® tablet
(Irbesartan/Hydrochlorothiazide 300mg/12.5mg)
& Approvel® tablet (Irbesartan 300mg)
From left-right: Cloxacillin 125mg/5ml
syrup & Ampicillin 125mg/ml syrup
Meet the Cillas Can you “Prove” it?
From left-right: Olanzepine 10mg tablet,
Olanzepine 5mg tablet, Olanzepine 10mg
orodispersible tablet & Olanzepine 5mg
orodispersible tablet
Oh my Zyprexa?
From left-right: L-thyroxine 25mcg tablet, L-
thyroxine 50mcg tablet & L-thyroxine 100mcg
tablet
The Euthyrox Trio
HPJ Pharmacy Bulletin Volume 2/ 2013
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The Oxycodone family
Diamicron MR what?
From left-right: Gliclazide 30mg MR
tablet & Gliclazide 60mg MR tablet
The Norditropins
From top-bottom: Somatropin 5mg/1.5mL
injection & Somatropin 10mg/1.5mL injection
The Rozidals
From left-right: Risperidone tablet 1mg
& Risperidone tablet 2mg
From left-right: Oxycodone 5mg tablet,
Oxycodone 10mg prolonged released tablet
& Oxycodone 20mg prolonged released
tablet
HPJ Pharmacy Bulletin Volume 2/ 2013
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Drug Names Confused Drug Names
Alprazolam Lorazepam
Aripiprazole Rabeprazole
Captopril Carvedilol
Januvia® Janumet
®
Isordil®
Plendil®
Lamivudine Lamotrigine
Lamotrigine Levothyroxine
Lorazepam Clonazepam
Metronidazole Metformin
Nystatin HMG-CoA reductase inhibitors (“statins”)
Olanzepine Quetiapine
Oxycodone Oxycontin
Simvastatin Sandostatin®
Carbimazole Albendazole
Ribavirin Minirin®
Potassium Citrate Potassium Chloride
Magnesium Trisilicate Magnesium Sulphate
Naloxone Maxolon®
Cinnarizine Cetrizine
Seroquel®
Seroquel XR®
Sound-Alike Medications
HPJ Pharmacy Bulletin Volume 2/ 2013
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References cited for all articles in this issue:
1. Wenman WM, Pagtakhan RD, Reed MH,
Chernick V, Albritton W. Adenovirus
bronchiolitis in Manitoba: epidemiologic,
clinical, and radiologic features. Chest. 1982
May; 81(5):605-9.
2. Centers for Disease Control and Prevention
(CDC). Adenoviruses: clinical overview,
diagnosis & prevention and treatment. 2011 Dec
27 [cited 2013 May 8]; Available from:
URL:http://www.cdc.gov/adenovirus/hcp/index.
html
3. Medscape References: Drugs, Diseases &
Procedures. Gompf SG, Dhanashree K, Oehler
R. Adenoviruses. 2012 Jun 5 [cited 2013 May 8];
Available from:
URL:http://emedicine.medscape.com/article/211
738-overview
4. Adenoviruses - Viruses that Affect Children
and Adults. 2012 Jan 27 [cited 2013 May 8];
Available from: URL:http://www.disabled-
world.com/health/influenza/adenoviruses.php#ix
zz2TGDkcOB3
5. Alharbi S, Van Caeseele P, Consunji-
Araneta R, Zoubeidi T, Fanella S, Souid AK,
Alsuwaidi AR. Epidemiology of severe pediatric
adenovirus lower respiratory tract infections in
Manitoba, Canada, 1991-2005.BMC Infect Dis.
2012 Mar 13;12:55.
6. Tabain I, Ljubin-Sternak S, Cepin-Bogovic
J, Markovinovic L, Knezovic I, Mlinaric-
Galinovic G. Adenovirus Respiratory Infections
in Hospitalized Children: Clinical Findings in
Relation to Species and Serotypes. Pediatr Infect
Dis J. 2012 Jul; 31(7):680-4.
7. Gavin PJ, Katz BZ. Intravenous ribavirin
treatment for severe adenovirus disease in
immunocompromised children. Pediatrics. 2002
Jul; 110(1 Pt 1):e9.
8. Fanourgiakis P, Georgala A, Vekemans M,
Triffet A, De Bruyn JM, Duchateau V.
Intravesical instillation of cidofovir in the
treatment of hemorrhagic cystitis caused by
adenovirus type II in a bone marrow transplant
recipient. Clin Infect Dis. Jan 1 2005; 40(1):199-
201.
9. Consensus with HOD Pediatrics and
Specialists from Hospital Tuanku Ja’afar,
Seremban.
10. Rebetol® [Prescribing Information]. USA:
Schering Corporation. 1998.
11. Copegus® [Prescribing Information]. UK:
Roche Products Limited. 2007.
12. Institute for Safe Medication Practices
(ISMP). ISMP's List of Confused Drug Names.
2011 June [cited 2013 May 8]; Available from:
URL:https://www.ismp.org/tools/confuseddrugn
ames.pdf
13. www.goldcopd.org/2013
14. http://ec.europa.eu/health
15. Ronald Dahl1, Kian Fan Chung: Chronic
obstructive pulmonary disease. Efficacy of a new
once-daily long-acting inhaled β2-agonist
indacaterol versus twice-daily formoterol in
COPD: Thorax 2010;65:473-479 (10.1136)
16. Mariom Cazzola,The effective treatment of
COPD: Anticholinergic: Drug Discovery Today
Therapeutic Strategies Vol. 3, No. 3 200
17. American society of hospital pharmacists.
ASHP guidelines on preventing medication
errors in hospitals. Am J Hosp Pharm.
1993;50:305-14
18. Giampaolo P. Velo, Pietro Minuz.
Medication errors: prescribing faults and
prescription errors. Br J Clin Pharmacol.
2009;67:6. 624-628
19. World Health organization. Look-alike
sound-alike medication names. May 2007;1:1.